Genetic counseling: Hemophilia and Von Willebrand Disease
Hemophilia and Von Willebrand Disease Hemophilia (- term to include hemophilia A (factor 8), hemophilia B (factor 9) and von Willebrand's Disease) Von Willebrand Disease (Vascular Hemophilia or pseudohemophilia) *Caused by lack of von Willebrand factor **Usually helps in the clotting process by binding to the surface of the wall and then making platelets bind to the surface of the blood vessel wall. Once they bind, it brings other platelets to clump on the surface=blood stops flowing and a clot is formed. **It is the thing that locates the platelets to the correct spot = affects platelet adhesion process. **People may have a smaller amount of protein produced or they have a change in function. **von Willebrand protein is also a carrier protein for Factor 8 = if it is not working properly you have decreased factor 8 as well. *Prevalence = up to 1/100 (1%) of the population *Characteristics - VARY even in families **Easy bruising is the major problem **Recurrent nosebleeds **Heavy menstrual cycles **Bleeding after surgery **Bleeding at delivery of a baby (during pregnancy you get increased vWf ) *Diagnosis **Best done by clinical diagnosis and family history **Also done by homeostasis screening tests (but they can be normal in mild cases) ***Bleeding time - a test that gets messed up by taking aspirin ***Antigenic levels of vWf - an immunoassay ****mild = 25-35% normal amount ****severe = <5% ****affected by blood type = A, B, AB have higher levels 48-240 u/dl and O have 36-160 u/dl. ***Platelet aggregation studies - only aggregation with ristocetin would be informative ***Von Willebrand factor activity = looks at ristocetin co-factor. Usually low if above is low. ***Von Willebrand multimers = look to see if the reason it is not functioning is because the larger multimers are not present. **Direct DNA testing for Type IIA or IIB **Problems with pregnancy, newborn period, times of stress or agitation *Inheritance **AR (severe or Type III) **AD (mild, Type IIA and IIB) **You can be a symptomatic or asymptomatic carrier depending on other factors. **Chromosome 12 *Treatment **Either drug or blood products - intravenously **Type I = DDAVP (Stimate) - synthetic agent that releases vWf from storage sites. Only works if there is some vWf present. **Type IIA = DDAVP **Type IIB = Humate-P or cryoprecipitate **Severe = Humate-P or cryoprecipitate **Platelet type = platelet concentrates **Factor 8 concentrates Do NOT work because they don't have enough vWf. *Lifestyle **Mild = treatment only before surgery **Severe = avoid taking aspirin and avoid activities with high risk of injury. Take Tylenol instead. Hemophilia A and B *Caused by decrease of lack of Factor 8 or 9 **Coagnulation is a process of activation of a variety of factors in sequence (I-XIII) **Deficiency in the factors can be Type I (reduced concentration) or Type II (defect in function) **Factor 8 is called the Antihaemophilic globulin **Factor 9 is the Christmas factor *Characteristics **Muscle or joint bleeding **<5% the normal value have spontaenous bleeding (esp. <2%) **>5% have bleeding after sugeries *Inheritance **X-linked recessive *Diagnosis **The two in indistinguishable clinically = they have to determined by specific factor assays. **Clotting factor assays Hemophilia A *Incidence 1/10,000 *Genetics/inheritance **X linked recessive **In 1/3 cases it is a new mutation **The gene is close to the tip Xq. **Heterogenetic *Values **plasma levels of factor 8: normal = 0.5-1.5 iu/ml **Carriers = 50% normal value typically (can be affected by lionization) **<.02 iu/ml = severe **0.02-0.05 iu/ml = moderate **>0.05 iu/ml = mild *Characteristics **spontaneous recurrent bleeding in the knees, elbows, ankles, shoulders (large joints and muscles!!!) **bleeding occurs 2-4 times per month **Starts around 6 months (mobility) **Can lead to lots of pain and loss of cartilage and osteoartrithis **There can be intrcranial bleeding = death in adults *Diagnosis **Reduced factor 8 **Normal vWf, Rcofactor, and bleeding time *Treatment **Provide Factor 8 concentrates to arrest bleeding immediately *Prenatal testing **Traditionally a two step process: sexing (by amnio at16 weeks) and then blood drawing(19-20 weeks) **CVS can be done with gene probes that have been determined by the mother and family prior to testing. Hemophilia B *Prevelance **1/5 that of Hemophilia A *Cause **Deficiency of Factor 9 which is Vitamin K dependant *Genetics/Inheritance **X-linked recessive *Characteristics **same as above *Treatment **Give frozen plasma **Give factor 9 concentrate *Values **Vary greatly but generally use above values for A Notes The information in this outline was last updated in 2000. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.